Hua Fang1, Hua-Feng Li2, Miao Yang1, Ru-Rong Wang3, Quan-Yun Wang3, Peng-Cheng Zheng4, Fang-Xiang Zhang1, Jian-Ping Zhang5. 1. Department of Anesthesiology, Guizhou Provincial People's Hospital, Guiyang, 550002, PR China; Department of Anesthesiology, Guizhou University People's Hospital, Guiyang, 550002, PR China. 2. Department of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu, 610041, PR China. 3. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, PR China. 4. Guizhou University Research Center for Analysis of Drugs and Metabolites, Guizhou University, Guiyang, 550025, PR China. 5. Department of Anesthesiology, Guizhou Provincial People's Hospital, Guiyang, 550002, PR China; Department of Anesthesiology, Guizhou University People's Hospital, Guiyang, 550002, PR China. Electronic address: albatrossa@126.com.
Abstract
OBJECTIVE: Hypoxic-ischemic brain damage (HIBD) is a major cause of acute mortality and chronic neurological morbidity in infants and children. Dexmedetomidine (DEX) is an effective choice in HIBD treatment. Recent findings have revealed that microRNA-128 (miR-128) is implicated in cerebral ischemia reperfusion. Hence, this study aimed to investigate the role of miR-128 in HIBD. METHODS: HIBD models of neonatal mice were established. HIBD mice were treated with DEX, and injected with agomir (ago)-miR-128 or antagomir (anti)-miR-128 into the lateral ventricles to explore the influence of miR-128 on the neuroprotective effects of DEX on HIBD. Subsequently, the mice body weight, left/right (L/R) brain weight ratio, left-brain water content as well as learning and memory abilities were measured. Furthermore, the pathological changes of brain tissues and apoptosis rate of nerve cells were determined. The potential relationship between miR-128 and WNT1 was analyzed. RESULTS: Over-expression of miR-128 caused an increase in mouse body weight, L/R brain weight ratio, and learning and memory abilities, while led to a decline in left-brain water content, brain tissue injury and apoptosis rate of nerve cells in DEX-treated HIBD mice. WNT1 was targeted and negatively regulated by miR-128. Silencing of WNT1 exerted the same effect as miR-128 on enhancing the neuroprotective effect of DEX on HIBD mice. CONCLUSION: Collectively, miR-128 enhanced neuroprotective effect of DEX on HIBD neonatal mice by inhibiting WNT1.
OBJECTIVE:Hypoxic-ischemic brain damage (HIBD) is a major cause of acute mortality and chronic neurological morbidity in infants and children. Dexmedetomidine (DEX) is an effective choice in HIBD treatment. Recent findings have revealed that microRNA-128 (miR-128) is implicated in cerebral ischemia reperfusion. Hence, this study aimed to investigate the role of miR-128 in HIBD. METHODS: HIBD models of neonatal mice were established. HIBD mice were treated with DEX, and injected with agomir (ago)-miR-128 or antagomir (anti)-miR-128 into the lateral ventricles to explore the influence of miR-128 on the neuroprotective effects of DEX on HIBD. Subsequently, the mice body weight, left/right (L/R) brain weight ratio, left-brain water content as well as learning and memory abilities were measured. Furthermore, the pathological changes of brain tissues and apoptosis rate of nerve cells were determined. The potential relationship between miR-128 and WNT1 was analyzed. RESULTS: Over-expression of miR-128 caused an increase in mouse body weight, L/R brain weight ratio, and learning and memory abilities, while led to a decline in left-brain water content, brain tissue injury and apoptosis rate of nerve cells in DEX-treated HIBD mice. WNT1 was targeted and negatively regulated by miR-128. Silencing of WNT1 exerted the same effect as miR-128 on enhancing the neuroprotective effect of DEX on HIBD mice. CONCLUSION: Collectively, miR-128 enhanced neuroprotective effect of DEX on HIBD neonatal mice by inhibiting WNT1.